Evidence for liver energy metabolism programming in offspring subjected to intrauterine undernutrition during midgestation

Maternal undernutrition programs fetal energy homeostasis and increases the risk of metabolic disorders later in life. This study aimed to identify the signs of hepatic metabolic programming in utero and during the juvenile phase after intrauterine undernutrition during midgestation. Fifty-three pregnant goats were assigned to the control (100% of the maintenance requirement) or restricted (60% of the maintenance requirement from day 45 to day 100 of midgestation and realimentation thereafter) group to compare hepatic energy metabolism in the fetuses (day 100 of gestation) and kids (postnatal day 90). Undernutrition increased the glucagon concentration and hepatic hexokinase activity, decreased the body weight, liver weight and hepatic expression of , , and mRNAs, and tended to decrease the hepatic glycogen content and mRNA level in the dams. Maternal undernutrition decreased the growth hormone (GH) and triglyceride concentrations, tended to decrease the body weight and hepatic hexokinase activity, increased the hepatic , and mRNAs levels and glucose-6-phosphatase activity, and tended to increase the hepatic and mRNAs levels in the male fetuses. In the restricted female fetuses, the hepatic hexokinase activity and mRNA level tended to be increased, but mRNA expression was decreased and the , , and mRNA levels tended to be decreased. Maternal undernutrition changed the hepatic metabolic profile and affected the metabolic pathway involved in amino acid, glycerophospholipid, bile acid, purine, and saccharide metabolism in the fetuses, but not the kids. Additionally, maternal undernutrition increased the concentrations of GH and cortisol, elevated the hepatic glucose-6-phosphate dehydrogenase activity, and tended to decrease the hepatic glycogen content in the male kids. No alterations in these variables were observed in the female kids. Maternal undernutrition affects the metabolic status in a sex- and stage-specific manner by changing the metabolic profile, expression of genes involved in glucose homeostasis and enzyme activities in the liver of the fetuses. The changes in the hormone levels in the male fetuses and kids, but not the female offspring, represent a potential sign of metabolic programming.